This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project 5: Inflammation During Obesity: Immune Responses to Gut Antigens in Mesenteric Fat Erik Eckhardt Obese individuals have greatly enlarged fat tissue, and they are also more likely to suffer from cardiovascular disease, diabetes, and other diseases. Interestingly, all these diseases carry an inflammatory component, and it has therefore long be suspected that fat tissues may have an effect on whole body inflammation. Indeed, recent work has clearly shown that fat tissues from obese individuals are often inflamed and release substances into the circulation that can cause inflammation elsewhere. What, then, causes fat tissues from obese individuals to be inflamed? The answer may lie in the intestine, because it is mostly fat tissue near the intestine, such as mesenteric fat, which is inflamed in obesity, whereas subcutaneous fat, while equally enlarged, often is not inflamed. We hypothesize that bacteria or bacterial products in the intestine enter mesenteric fat tissue when obese individuals ingest high fat meals, because large amounts of dietary fat can induce leakiness in the intestine. Our data with mice so far suggest that this is indeed the case. If we confirm these data and our hypothesis in general, we can then look at how to reduce the number of pro-inflammatory bacteria in the intestine that cause fat tissue inflammation.